Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 10;23(6):2973.
doi: 10.3390/ijms23062973.

A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs

Masayuki Miyagi  1   2 , Kentaro Uchida  1   2 , Sho Inoue  1 , Shotaro Takano  1 , Mitsufumi Nakawaki  1 , Ayumu Kawakubo  1 , Hiroyuki Sekiguchi  2 , Toshiyuki Nakazawa  1 , Takayuki Imura  1 , Wataru Saito  1 , Eiki Shirasawa  1 , Akiyoshi Kuroda  1 , Shinsuke Ikeda  1 , Yuji Yokozeki  1 , Yusuke Mimura  1 , Tsutomu Akazawa  3 , Masashi Takaso  1 , Gen Inoue  1
Affiliations

A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs

Masayuki Miyagi et al. Int J Mol Sci. .

Abstract

Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP's pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (-) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (-) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.

Keywords: calcitonin gene-related peptide; discogenic low back pain; microsomal prostaglandin E synthase-1.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relationship between mechanical stress on intervertebral discs and pain-related molecule expression.
Figure 2
Figure 2
Measurement parameters for evaluating spinal instability. (A) Percentage slippage (%slip), (B) dynamic translation, which was the difference in segmental slippage between the flexion and extension positions (Translation), (C) the slippage angle in the flexion position (Slip angle), and (D) the vacuum phenomenon (VP) on sagittal views of computed tomography scans were measured.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Hoy D., Bain C., Williams G., March L., Brooks P., Blyth F., Woolf A., Vos T., Buchbinder R. A systematic review of the global prevalence of low back pain. Arthritis Rheum. 2012;64:2028–2037. doi: 10.1002/art.34347. - DOI - PubMed
    1. Dagenais S., Caro J., Haldeman S. A systematic review of low back pain cost of illness studies in the United States and internationally. Spine J. 2008;8:8–20. doi: 10.1016/j.spinee.2007.10.005. - DOI - PubMed
    1. Takura T., Ushida T., Kanchiku T., Ebata N., Fujii K., DiBonaventura M., Taguchi T. The societal burden of chronic pain in Japan: An internet survey. J. Orthop. Sci. 2015;20:750–760. doi: 10.1007/s00776-015-0730-8. - DOI - PubMed
    1. Suzuki H., Kanchiku T., Imajo Y., Yoshida Y., Nishida N., Taguchi T. Diagnosis and Characters of Non-Specific Low Back Pain in Japan: The Yamaguchi Low Back Pain Study. PLoS ONE. 2016;11:e0160454. doi: 10.1371/journal.pone.0160454. - DOI - PMC - PubMed
    1. Burke J.G., Watson R.W., McCormack D., Dowling F.E., Walsh M.G., Fitzpatrick J.M. Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J. Bone Jt. Surg. Br. 2002;84:196–201. doi: 10.1302/0301-620X.84B2.0840196. - DOI - PubMed